Transcatheter heart valve thrombosis

Transcatheter heart valve thrombosis Jeroen J Bax Dept Cardiology Leiden, The Netherlands New York, 2017 The department of Cardiology of the Leiden University Medical center received research grants from Boston Scientific, Biotronik, Medtronic and Edwards Lifesciences

When everything was simple: AV mean gradient after TAVR PARTNER 1-cohort A Mack et al. Lancet et al 2015

When everything was simple: EROA after TAVR PARTNER 1-cohort A Mack et al. Lancet et al 2015

TIA stroke rate Between 1 and 2 years, 8 strokes occurred (4 in the TAVR group and 4 in the surgery group) and 3 transient ischemic attacks (2 in the TAVR group and 1 in the surgery group). PARTNER 1-cohort A Kodali et al. NEJM 2012

CT post-tavr however showed. hypo-attenuated leaflet thickening (HALT) with or without restricted leaflet motion (HAM) (2D and 4D) suggesting thrombosis..

Normal: CT vs Echo (mean 8 mmhg)

Abnormal: CT vs Echo (mean 38 mmhg)

One of the first studies N = 156, 46% male TAVI with SAPIEN 3 THV CT 5 days (median) after TAVI HALT 10.3% of patients Echo 5 days (median) after TAVI mean gradient 8±3.5 mmhg Pache et al Eur Heart J 2016

Some show: Matched anatomy and (dys)function Mean gradient 25 mmhg

But most show: Mismatch anatomy and function Mean gradient 11 mmhg

What is in the literature? 12 studies Author (year) No Prevalence of thrombosis on MDCT (time) Prevalence of thrombosis on Echo (time) Mean gradient (mmhg) - EOA (cm 2 ) Latib et al (2015) 4266 NA 0.61% (median 181 days) Pacheet al (2016) 156 10.6% (median 5 days) NA (median 5 days) 40.5±14.0 - NA 8±3.5 - NA Leetmaa et al(2016) 140 4% (1-3 months) NA (1-3 months) 19.2 1.44 Del Trigo et al (2016) 1521 NA 4.5% (4 years) 26.1±11 - NA Hansson et al (2016) 405 7% (1-3 months) NA (1-3 months) 10±7-1.5±0.5 Makkaret al (2015) 55 40% (median 32 days) Makkaret al (2015) 132 13% (median 86 days) Yanagisawa et al(2017) 70 14.3% (1 year) Chakravarty et al (2017) 752 13% (median 58 days) Vollemaet al (2017) 434 12% (median 35 days) NA (30 days) NA (30 days) 9.2±4.9 - NA 8.4±2.9 - NA NA (1 year) 8.3±0.8-1.03±0.25 6% (median 58 days) 13.8±10.0 - NA 3% (3years) 9.3±4.7-1.99± 0.56 Jose et al (2017) 642 9/10 (NA) 2.8% (median 181 days) 34±14-1.06±0.46 Sondergaard et al (2017) 61 11% (140±152 days) NA 7.0±3.2 - NA

What the literature tells us Author (year) No Prevalence of thrombosis on MDCT (time) Prevalence of thrombosis on Echo (time) Mean gradient (mmhg) - EOA (cm 2 ) Latib et al (2015) 4266 NA 0.61% (median 181 days) Pacheet al (2016) 156 10.6% (median 5 days) NA (median 5 days) 40.5±14.0 - NA 8±3.5 - NA Leetmaa et al(2016) 140 4% (1-3 months) NA (1-3 months) 19.2 1.44 Del Trigo et al (2016) 1521 NA 4.5% (4 years) 26.1±11 - NA Hansson et al (2016) 405 7% (1-3 months) NA (1-3 months) 10±7-1.5±0.5 Makkaret al (2015) 55 40% (median 32 days) Makkaret al (2015) 132 13% (median 86 days) Yanagisawa et al(2017) 70 14.3% (1 year) Chakravarty et al (2017) 752 13% (median 58 days) Vollemaet al (2017) 434 12% (median 35 days) NA (30 days) NA (30 days) 9.2±4.9 - NA 8.4±2.9 - NA NA (1 year) 8.3±0.8-1.03±0.25 6% (median 58 days) 13.8±10.0 - NA 3% (3years) 9.3±4.7-1.99± 0.56 Jose et al (2017) 642 9/10 (NA) 2.8% (median 181 days) 34±14-1.06±0.46 Sondergaard et al (2017) 61 11% (140±152 days) NA 7.0±3.2 - NA

N = 4266 26 (0.61%) THV thrombosis Median time to diagnosis 181 days 65% worsening dyspnea 31% subclinical (asymptomatic) No neurological events No thromboembolic events Mean aortic valve gradient 40.5±14.0 mmhg Anticoagulation effective treatment Latib et al. Circ Cv Intervent 2015

Latib et al. Circ CV Intervent 2015 Gradient vs anti-coagulation

N = 1521 68 (4.5%) Valve hemodynamic deterioration (VHD) Assessed with echocardiography. VHD was defined as a 10 mmhg increase in transprosthetic mean gradient during follow-up compared with discharge assessment. Follow-up 4 years Del Trigo et al. JACC 2016

What the literature tells us 12 studies Author (year) No Prevalence of thrombosis on MDCT (time) Prevalence of thrombosis on Echo (time) Mean gradient (mmhg) - EOA (cm 2 ) Latib et al (2015) 4266 NA 0.61% (median 181 days) Pacheet al (2016) 156 10.6% (median 5 days) NA (median 5 days) 40.5±14.0 - NA 8±3.5 - NA Leetmaa et al(2016) 140 4% (1-3 months) NA (1-3 months) 19.2 1.44 Del Trigo et al (2016) 1521 NA 4.5% (4 years) 26.1±11 - NA Hansson et al (2016) 405 7% (1-3 months) NA (1-3 months) 10±7-1.5±0.5 Makkaret al (2015) 55 40% (median 32 days) Makkaret al (2015) 132 13% (median 86 days) Yanagisawa et al(2017) 70 14.3% (1 year) Chakravarty et al (2017) 752 13% (median 58 days) Vollemaet al (2017) 434 12% (median 35 days) NA (30 days) NA (30 days) 9.2±4.9 - NA 8.4±2.9 - NA NA (1 year) 8.3±0.8-1.03±0.25 6% (median 58 days) 13.8±10.0 - NA 3% (3years) 9.3±4.7-1.99± 0.56 Jose et al (2017) 642 9/10 (NA) 2.8% (median 181 days) 34±14-1.06±0.46 Sondergaard et al (2017) 61 11% (140±152 days) NA 7.0±3.2 - NA

N = 140 5 (4%) THV thrombosis MDCT performed within 1-3 months of TAVI N = 1 heart failure symptoms N= 4 subclinical (asymptomatic) No neurological events No thromboembolic events Mean aortic valve gradient <20 mmhg in all Anticoagulation effective treatment Leetmaa et al. Circ Cv Intervent 2015

N = 55 TAVI clinical trial 22 (40%) N = 132 registry (TAVR or SAVR) 17 (13%) THV thrombosis Median time to MDCT: 32-86 days Mean gradient <20 mmhg in all patients Anticoagulation effective treatment Makkar et al. New Engl J Med 2016

N = 128 16 (12%) THV thrombosis Assessed with MDCT median follow-up of 35 days Mostly asymptomatic ( 1 patient with heart failure) Mean gradient 9.3±4.7 mmhg No association with increased risk of TIA and all strokes Vollema et al. Eur Heart J 2017

COHORT OF THV 11% THV thrombosis scan 1 = 140 (STD 152) days scan <12 MONTHS First important observation: progression absent in all patients using anticoagulation. Second important observation: 61.9% of patients - normal valves at both 4D CT scans despite absence of oral anticoagulation. Third important observation: stability also noted in 41 patients using antiplatelet therapy (or no therapy). Implying that anticoagulation may not be warranted in all patients, but should be personalized to patients who need it. Sondergaard et al. Eur Heart J 2017

The definitions Echocardiography: Zoghbiet al (JASE 2009): definition for surgical bioprosthetic valve prostheses Possible stenosis: mean gradient 20-35 mmhg effective orifice area (indexed for body surface area) 1.2-0.8 cm2. Significant stenosis: mean gradient >35 mmhg effective orifice area (indexed for body surface area) <0.8 cm2. expanded by Lancellotti et al (EHJCVI 2016): possible obstruction: increase in mean gradient at follow-up between 10-19 mmhg significant obstruction: increase in mean gradient at follow-up 20 mmhg.

The definitions CT: hypo-attenuated leaflet thickening (HALT) 2D with or without restricted leaflet motion 4D

Need for better definitions Dangas et al recently stated that prosthetic heart valve dysfunction can be seen as a continuum of the same pathological process with early thrombus formation (CT), later fibrotic pannus formation (echo), followed by degeneration / dysfunction (echo) JACC 2016

Open questions: Correlation between thrombosis rate based on imaging vs. stroke rate 10-15% 3-5% 5-7% HALT - CT Echocardiography Stroke/TIA

Open questions: Resolution after anticoagulation Everyone anticoagulation? How long? When to start? (but a significant number of patients has indication) Imaging surveillance? When? How often? Which technique?

Source: https://www.medscape.org/viewarticle/864130_transcript

Source: https://www.medscape.org/viewarticle/864130_transcript